The regulation of the family of UDP glucuronosyltransferase enzymes is being studied by means of DNA, RNA and protein chemistry. Different members of the transferase system are known to be induced by a number of different types of effector compounds; two such compounds used in these studies are phenobarbital and 3-methylcholanthrene (3MC). Five mouse transferase cDNA clones have been isolated and shown to be 85% homologous by nucleotide sequence analysis and cross-hybridization studies. These clones represent members of a subfamily and possess unique sequences in their 3' regions. The pUDPGTm-1 (1800-bp insert) and pUDPGTm-2 (1600-bp insert) differ by one nucleotide (converting an isoleucine to methionine). A third clone, pUDPGTm-3, contains an unusually long insert with 4300 bp compared to other transferase cDNAs which encode mRNAs ranging from 1900 to 3000 nucleotides. The detection of 35 genomic clones (inserted into Gamma EMBL-3) with sequence homology to pUDPGTm-1 suggests that multiple and closely related genes exist and that the gene for pUDPGTm-1 is most likely duplicated. At least two of these clones encode proteins with 50-kDa molecular weights, have one or two potential glycosylation sites, and contain hydrophobic transmembrane amino acid sequences near the carboxy terminus. In order to study 3MC-inducible transferase forms, a cDNA library was recently constructed in Gamma gt11 using 3MC-induced mRNA. This library is being screened with previously developed mouse transferase antibody. Also, human mRNA has been isolated and translated in vitro to produce a 48-kDa protein immunoprecipitable by mouse transferase antibody. A human cDNA library has been constructed and successfully probed with the insert from pUDPGTm-1 to isolate and partially purify two human transferase cDNA clones. A human transferase form is being purified which appears to have similar properties to a mouse 3MC-inducible form.